Natalia V. Beloborodova

By Beloborodova Natalia Vladimirovna

The majority of species of the human gut microbiota is not cultivated on artificial nutrient media, but they are included in the functioning of microbial metabolic conveyor. Between the numerous gut bacteria (transmitter) and billions of intracellular mitochondria (receiver), the function of signaling molecules performs aromatic metabolites. Sepsis destroys the coordinated work of the indigenous anaerobic microflora. This leads to the imbalance of aromatic microbial metabolites (AMM). We hypothesized and proved diagnostic and pathogenic significance of this. First, deficiency of the end products of microbial metabolism—lipophilic AMM (PhPA and derivatives‐cinnamic and benzoic acids) in sepsis, and second, excessive accumulation in blood of intermediate products named, “sepsis‐associated” AMM—both lead to the development of mitochondrial dysfunction. Particularly, the total suppressed production of mROS can manifest by “hibernate‐like state” of cells and lead to MOF. The participation of aromatic metabolites in the development of septic shock can be explained by the inhibition of tyrosine hydroxylase and impaired synthesis of catecholamines. In clinical research, the high levels of “sepsis‐associated” AMM (p‐HPhAA, p‐HPhLA, and PhLA) correlate with the severity according to APACHE II, Sepsis-related Organ Failure Assessments (SOFA) score and mortality. To improve the survival of ICU patients, requires more attention to the role of imbalance of microbial metabolites in sepsis.

Part of the book: Sepsis

By Natalia V. Beloborodova, Andrey V. Grechko and Andrey Yu Olenin

In the twenty-first century, metabolomics allowed evaluating the profile of metabolites of various classes of compounds in the human body. The most important achievement of the metabolic approach is to obtain evidence of the intersection of human biochemical pathways and its microbiota. The effect of certain microbial metabolites on the work of key enzymes involved in the biotransformation of amino acids and other substances becomes more important in patients at risk of developing neurological and mental disorders and also contributes to the development of life-threatening conditions up to multiple organ failure after operations, injuries, and serious diseases. The authors of this chapter call the microbiota an “invisible organ,” emphasizing its functional significance, and not just taxonomy, as previously thought. This chapter will discuss the mutually beneficial integration of the metabolome/microbiome in the body of healthy people and will focus on the effects of microbiota dysfunction.

Part of the book: Metabolomics

By Ekaterina Chernevskaya and Natalia Beloborodova

When diagnosing sepsis, it is common to look for pathogens, microbe’s DNA, lipopolysaccharide (LPS), or host biomarkers while missing out on microbiota. The next-generation sequencing of 16S rRNA gene allowed characterizing the gut microbiota taxonomy and clarifying the gut microbial population being more complex than was previously thought. We suppose that significant disruption of the microbiota is an indicator of the major role it plays in sepsis. Serious metabolic disorders of the gut microbiota may contribute to an unfavorable outcome in septic patients. With the changes not only in the composition but also in the metabolic activity of the gut microbiota taken into account, the characteristics of the mechanisms of interactions in the “septic” microbiome will allow the advances in the optimization of the diagnostics and therapy of sepsis to be made.

Part of the book: Infectious Process and Sepsis

By Natalia Beloborodova and Andrey Grechko

In conditions of severe gut dysbiosis, there is a risk of developing diseases of the host organism in general and of the brain in particular, as evidenced by a growing number of studies. This chapter focuses on several groups of low-molecular-weight compounds that originate primarily from the gut microbiota. It discusses the results of experimental and clinical studies on the effect of microbial metabolites (such as short-chain fatty acids, phenolic metabolites of tyrosine, indolic metabolites of tryptophan, trimethylamines) on the brain. Several studies have proven that the microbial metabolite profiles in the gut and serum are interlinked and reflect a disruption of the gut microbial community. Using 16S ribosomal RNA gene sequencing, it was found that the gut microbiota of patients with positive or negative dynamics of neurological status differ taxonomically. The chapter also presents data obtained from animal germ-free (GF) models. Many researchers would like to consider the gut microbiota as a new therapeutic target, including for the treatment of brain diseases, stroke prevention, reduction of neuroinflammation, and more successful neurorehabilitation of patients.

Part of the book: Human Microbiome